We have recently demonstrated the existence of marked alterations in immunological competence in two experimental models of diabetes mellitus: the C57Bl/KsJ-db plus/db plus mice and the streptozotocin-induced diabetic C57BL/6 mice. These studies, which are the first comprehensive evaluation of immunological function in experimental diabetes, should provide major insights into the biochemical and functional consequences of the diabetic state on immunological reactivity and, additionally, should provide important insights into the hormonal regulation of immunological function. These investigations may also provide a useful model for the elucidation of the functional consequences of the diabetic state on cells of other organ systems. The objectives of this proposal are to extend our previous observations in two specific areas: 1. We shall demonstrate whether the alterations in immunological function which occur in experimental diabetes mellitus are a direct consequences of the abnormal in vivo metabolic milieu or whether they result from an intrinsic defect in the lymphoid cells themselves. 2. We shall further define the exact nature of the immunological alterations occurring in diabetic mice. Specifically we will examine the generation and effector cell function of two T cell subpopulations which appear to be abnormal in diabetic mice - cytotoxic T cells and suppressor T cells.